Hookah Additive Research to Inform Product Standards (HARPS)

Waterpipe Tobacco Additives and Their Effect on Human Puffing Behavior, Toxicant Exposures, Pulmonary Function, and Appeal

This clinical trial evaluates how the content of waterpipe (WP) tobacco affects the appeal, puffing behavior, and toxicity of WP tobacco smoking. The data from the proposed study will provide direct links between WP tobacco's primary additives (sugars and humectants), CO and nicotine biomarkers, smoker preferences, perceptions of harm and puffing behaviors, and the subsequent range of toxicant exposures associated with these additives and behaviors. Study outcomes include waterpipe puffing behaviors, exhaled carbon monoxide levels, nicotine uptake, spirometry, sensory perceptions, smoking appeal, and risk perception. Waterpipe tobacco smoking is often the first combustible tobacco product tried by adolescents and young adults, possibly due to the widespread availability of heavily sweetened waterpipe tobacco and the perception that waterpipe smoking is a safer alternative to cigarette smoking. However, waterpipe tobacco smoking is associated with lung disease, carbon monoxide poisoning, and precursor conditions for oral and other cancers in adolescents and young adults. There is currently little data available on how the primary additives (by weight) in waterpipe tobacco affect puffing behaviors, toxicant exposures, pulmonary function and appeal. This clinical trial uses established waterpipe tobacco smokers, four investigational tobacco products with precisely manipulated levels of humectants and natural sugars in a single-blind, crossover (repeated measures) study design to determine how waterpipe tobacco additives effect human puffing behavior, nicotine uptake, flavor perceptions, lung function, and biomarkers of exposure.

Study Overview

• Status: Completed
• Conditions: Tobacco-Related Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Behavioral: Tobacco Smoking

Detailed Description

Currently there are no regulations governing the content of WP tobacco. Because mandated changes in tobacco content may lead to unintended consequences that ultimately result in public health declines, human use behaviors must be well understood prior to implementing regulatory product standards. The proposed study will include preparing and characterizing the content of 4 investigational tobacco products (ITPs) (Aim 1); characterizing the mainstream smoke toxicant emissions from machine smoking the 4 ITPs using a single, established puffing regimen (Aim 2); measuring human puffing behavior, general harm and specific health risk and flavor perceptions, lung function, and biomarkers of exposure in a group of established WP smokers smoking the 4 ITPs in the laboratory (Aim 3), and estimating toxicant exposure ranges using machine smoking and puffing regimens derived from the human laboratory testing (Aim 4).

The clinical trial (Aim 3) will focus on using a group of established adult and young adult WP smokers, a cross-over study design, CO and nicotine biomarkers, spirometry, cutting edge psychophysical measurement tools, and risk perception instruments to map the relationship between sensory experiences and preferences of sweetness and flavor to specific additive content in WP tobacco that affect these experiences, preferences, acute health effects, and toxicant exposures. Study subjects will participate in a series of 4 clinic sessions, each visit separated by at least a week, in which they smoke one of 4 tobacco preparations (single-blind) using a research grade waterpipe in a randomly assigned sequence in a smoking room with sufficiently controlled ventilation rate to keep ambient air CO levels below 25 ppm. Exhaled CO, whole blood samples and spirometry measures will be collected before and immediately after the smoking session. Taste perceptions, liking/disliking, and risk perceptions will be determined via questionnaires before, during, and after smoking.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Sufficient understanding of consent form and study procedures
• Age 21-50 years old
• Experienced WP smokers defined as having smoked a WP at least 3 times per month in the last month
• Willing/able to abstain from nicotine product use for at least 12 hours prior to the laboratory visits
• Willing to attend four laboratory sessions at the same time of day lasting approximately 3 hours (h) each
• Read and speak English

Exclusion Criteria:

• Evident intoxication on any visit
• Exhaled breath CO > 10 ppm
• Pregnancy (known or suspected), trying to become pregnant, breastfeeding, unwillingness to use contraception for the duration of the study
• Significant smoking-related disease (by history)

• Any of the following in the past 30 days (self-report):

  • Uncontrolled asthma or asthma that is worse than usual
  • Severe respiratory allergies, such as wheezing, coughing, shortness of breath when exposed to known allergens
  • Acute upper or lower respiratory illnesses like the flu, common cold, or pneumonia
  • Any other serious lung infection or disease, such as tuberculosis, cystic fibrosis, or lung cancer
  • Hospitalization for difficulty breathing
• Currently engaging in a WP tobacco smoking quit attempt

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tobacco flavor preparation; High Sweetness, High Humectant (tobacco smoking); Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered.	Other: Questionnaire Administration; Ancillary studies; Behavioral: Tobacco Smoking; Smoke waterpipe tobacco; Other Names: Smoking; Tobacco, Smoking
Experimental: Tobacco flavor preparation; High Sweetness, Medium Humectant (tobacco smoking); Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered.	Other: Questionnaire Administration; Ancillary studies; Behavioral: Tobacco Smoking; Smoke waterpipe tobacco; Other Names: Smoking; Tobacco, Smoking
Experimental: Tobacco flavor preparation; Medium Sweetness, High Humectant (tobacco smoking); Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered.	Other: Questionnaire Administration; Ancillary studies; Behavioral: Tobacco Smoking; Smoke waterpipe tobacco; Other Names: Smoking; Tobacco, Smoking
Experimental: Tobacco flavor preparation; Medium Sweetness, Medium Humectant (tobacco smoking); Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered.	Other: Questionnaire Administration; Ancillary studies; Behavioral: Tobacco Smoking; Smoke waterpipe tobacco; Other Names: Smoking; Tobacco, Smoking

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Exhaled Breath Carbon Monoxide (CO)	Change from baseline exhaled breath carbon monoxide (boost). CO was collected before and immediately after each smoking session with a handheld electrochemical cell.	Approximately 30 to 90 minutes
Change in Plasma Nicotine	Change from baseline plasma nicotine (boost): Whole blood was collected before and immediately after each smoking session, separated, and plasma layer transferred and stored at -80 °C until analysis for nicotine according to validated methods using LC-MS/MS.	Approximately 30 to 90 minutes
Change in Forced Vital Capacity (FVC)	Spirometer measurements will be collected - change in forced vital capacity (FVC) (post-pre).	Approximately 30 to 90 minutes
Change in Forced Expiratory Volume in 1 Second (FEV1)	Spirometer measurements will be collected - change in forced expiratory volume in 1 second (FEV1) (post-pre)	Approximately 30 to 90 minutes
Change in FEV1/FVC; The Ratio of the Forced Expiratory Volume in the First One Second to the Forced Vital Capacity of the Lungs.	Spirometer measurements will be collected - change in FEV1/FVC, the ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs (post-pre).	Approximately 30 to 90 minutes
Change in Peak Expiratory Flow (PEF)	Spirometer measurements will be collected - change in peak expiratory flow (PEF) (post-pre).	Approximately 30 to 90 minutes
Change in Forced Expiratory Flow at 25-75% of FVC	Spirometer measurements will be collected - change in forced expiratory flow at 25-75% of FVC (post-pre).	Approximately 30 to 90 minutes
Tobacco Use History	Ever use of tobacco products, assessed at the first study visit	Baseline
Nicotine Dependence (HONC)	Hooked on Nicotine Checklist (HONC) comprised of 10 "Yes" or "No" questions, assessed on the first study visit. Scores range from 0 to 10 with higher scores indicating greater nicotine dependence.	Baseline
Nicotine Dependence (LWDS)	Lebanese Waterpipe Dependence Scale (LWDS) comprised of twelve questions and assessed on the first study visit. LWDS values range from 0 to 36 where higher sores indicate greater nicotine dependence.	Baseline
General Harm and Health Risk Perceptions	Assessed using harm/health risk perceptions questionnaire. General harm is rated after the smoking session on a scale from 0 (no harm) to 10 (extreme harm) with higher scores indicating a greater perceived harm/health risk.	Post Smoking Session
Subjective Effects of Smoking Tobacco	Direct Effects of Tobacco scale; the scale for each effect ranges from 0 (not at all) to 100 (extremely) with higher ratings indicating a greater effect of the tobacco.	Post Smoking Session
Change in Subjective Effects of Smoking Tobacco - Direct Effects of Nicotine	Change in Direct Effects of Nicotine scale from baseline (post - pre). The scale for each effect ranges from 0 (not at all) to 100 (extremely) with higher ratings indicating a greater effect of the tobacco.	Approximately 30 to 90 minutes
Change in Subjective Effects of Smoking Tobacco (QSU)	Change from baseline Questionnaire for Urges to Smoke (post - pre). This is a 10-item measure where participants rate smoking-related items on a 6-point Likert scale ranging from 1 (strongly disagree) to 6 (strongly agree). Items are collapsed into two previously identified factors (Factor 1: strong desire and intention to smoke; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 30 with higher scores indicating greater urge to smoke.	Approximately 30 to 90 minutes
Change in Nicotine Withdrawal Assessment (MNWS)	Change from baseline using Waterpipe-modified Minnesota Withdrawal Scale (post - pre). The scale ranges from 0 (not at all) to 100 (extremely) with higher total numbers meaning greater withdrawal symptoms.	Approximately 30 to 90 minutes
Tobacco Flavor Perception (gLMS)	To determine the relative intensity of specific flavors, e.g., sweetness, the general version of the Labeled Magnitude Scale (gLMS) was used post-smoking session. The scale ranges from 0 to 100 where higher scores indicate that the perception is stronger.	Post Smoking Session
Tobacco Flavors Perception, Degree of Liking or Disliking (LHS)	To assess the degree of liking or disliking of flavors, will use the Labeled Hedonic Scale (LHS) to collect ratio-level data on the magnitude of liking and disliking of sensation post-smoking session. Scores range from 0 to 100 with higher scores indicating greater liking.	Post Smoking Session
Puffing Topography - Puff Volume	Puff volume measured continuously during the smoking session using the research-grade waterpipe.	Up to 60 minutes
Puffing Topography - Puff Duration	Puff duration measured continuously during the smoking session using the research-grade waterpipe.	Up to 60 minutes
Puffing Topography - Flow Rate	Puffing average flow rate measured continuously during the smoking session using the research-grade waterpipe.	Up to 60 minutes
Puffing Topography - Peak Flow Rate	Puffing peak flow rate measured continuously during the smoking session using the research-grade waterpipe.	Up to 60 minutes
Puffing Topography - Interpuff Interval	Interpuff interval measured continuously during the smoking session using the research-grade waterpipe.	Up to 60 minutes

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Ohio State University; Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Marielle C Brinkman, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2022
• Primary Completion (Actual): May 11, 2023
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: OSU-22158; NCI-2022-05156 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA255563 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No